Composition containing gel

ABSTRACT

A new plastic composition which is slow dissolving in aqueous media and can be used to slowly release medication or other additive ingredients in an aqueous environment, which plastic composition is prepared by cross-linking a hydrophilic colloid such as carboxymethyl cellulose gum or alginate gum with a crosslinking agent, usually a polyol such as propylene glycol, in a relatively nonreactive water soluble carrier such as glycerol. The total composition, including the carrier, sets up into a plastic gel, the consistency of which can be varied by varying proportions of ingredients. The reaction can be speeded or driven to a more completely cross-linked state by using a catalysts such as aluminum or calcium salts. Complexing agents can be included for complexing the catalysts and releasing it slowly throughout the reaction to slow the reaction down where desired. Generally, the reaction proceeds faster in a close to neutral or basic medium at pH&#39;&#39;s ranging up to 10 or 11 and slower in an acid medium at pH of 5 and below so the rate of reaction can be controlled by adjusting the pH. Usually the composition will contain medication or cosmetic additives or ingredients and it can be molded by extrusion or the like into any predetermined form, e.g., in the form of a ring. In a preferred form, the composition has excellent pressure sensitive adhesive properties and these properties are very pronounced where the hydrophilic colloid used is carboxymethyl cellulose.

Unite tates stem Etes [54] COMPOSITION CONTAINING GEL Donald E. Etes,Crystal Lake, 111. v

[73] Assignee: Holllster Incorporated [22] Filed: Feb. 24, 1970 [21 1Appl. No.: 13,608

[72} Inventor:

[52] US. CL ..l06/l70, 106/189, 106/197 CM,

3,079,303 2/ 1963 Raff et a]. ..424/33 3,279,996 10/1966 Long et al....424/32 3 302,647 2/1967 Marsan 128/283 FOREIGN PATENTS OR APPLICATIONSCanada ..424/ 32 Feb. 8, 1972 [57] ABSTRACT A new plastic compositionwhich is slow dissolving in aqueous media and can be used to slowlyrelease medication or other additive ingredients in an aqueousenvironment, which plastic composition is prepared by cross-linking ahydrophilic colloid such as carboxymethyl cellulose gum or alginate gumwith a I cross-linking agent, usually a polyol such as propylene glycol,T in a relatively nonreactive water soluble carrier such as glycerol.The total composition, including the carrier, sets up into a plasticgel, the consistency of which can be varied by varying proportions ofingredients. The reaction can be speeded or driven to a more completelycross-linked state by using a catalysts such as aluminum or calciumsalts. Complexing agents can be included for complexing the catalystsand releasing it slowly throughout the reaction to slow the reactiondown where desired. Generally, the reaction proceeds faster in a closeto neutral or basic medium at pHs ranging up to 10 or 11 and slower inan acid medium at pH of 5 and below so the rate of reaction can becontrolled by adjusting the pH. Usually the composition will containmedication or cosmetic additives or ingredients and it can be molded byextrusion or the like into any predetermined form, e.g., in the form ofa ring. In a preferred form, the composition has excellent pressuresensitive adhesive properties and these properties are very pronouncedwhere the hydrophilic colloid used is carboxymethyl cellulose.

M Claims, 4 Drawing Figures PATENTEDFEB v 8 1212 ova? 8 MINUTES INFCOMPOSITION CONTAINING GEL BACKGROUND OF THE INVENTION 1. Field of theInvention This invention relates to solidified plastic compositions 5sorbed by the body but remains in the body intact, creatingcomplications later.

Karaya has been used as a healing powder to thicken glycerine or thelike and form gellike materials for use as sealing rings or the like,e.g., around stoma. See U.S. Pat; No.

3,302,647 issued to Arthur E. Marsan on Feb. 7, l967.'However, Karaya isa nutrient substance which is capable of supporting substantialbacterial or other growth and in some uses this can be undesirable.Also, it has been found that gels containing Karaya do not dissolve asreadily as they should for optimum use in releasing medication or thelike. Karaya gels also have limited shelf life, hardening after storagefor an extended period under ambient conditions.

SUMMARY OF THE INVENTION This invention provides a plastic or gelproduct which slowly dissolves in an aqueous medium and can be used forslowly releasing additives, such as medications, over an extended periodof time. The invention further relates to a method of making such aplastic or gel product.

The product basically is a slowly water-soluble gel which functions as acarrier for the additive to be released. In the preferred form, thegelling agent in the gel is a nutrient-free" reaction product of ahydrophilic colloid and a polyol which cross-links the colloid. Thecross-linked reaction product is formed in a water-soluble liquidorganic medium and the entire reaction mass including the liquid mediumis gelled by reacting the colloid with the polyol in the presence of theliquid medium. The gelling agent entraps the liquid medium where aviscous, elastomeric or solid gel, usually soft" solid, is formed or canbe diluted somewhat by the liquid medium or other diluents where a morefluid consistency is desired, e.g., as a base for a lotion. The gelledproduct is slowly, but completely, soluble in an aqueous medium over anextended period of time. It is soluble in mammal body fluids and can beassimilated by the body.

While an illustrative embodiment of the invention is shown in thedrawings and will be described in detail herein, the invention issusceptible of embodiment in many different forms and it should beunderstood that the present disclosure is to be considered as anexemplification of the principles of .the-invention and is not intendedto limit the invention-tothe embodiment illustrated.

BRIEF DESCRIPTION OF THE DRAWINGS DESCRIPTION OF THE PREFERREDEMBODIMENT Turning first to FIGS. 1- through 3, a molded plastic mass orring 12 is shown molded in situ and contained within container '14 inthe form of a ring. A suitable cover 16 is provided'for container 14 andcan be hingedly secured to container 14 by means of a tape as at 18. Thecontainer 14 and cover 16 can be sealed closed along their seam line tomaintain the molded plastic mass or ring 12 in a sterile condition, ifdesired.

The plastic mass 12 is composed of the reaction product of anutrient-free" hydrophilic colloid, usually particulate or powdered, anda cross-linking agent, usually a liquid polyol, in the presence of asuitable nutrient-free organic liquid medium such as glycerin. The termnutrient-free" as used herein is intended to define materials which haveno nutrient value or have a nutrient value at a controllable level whichcan be used for support of controlled amounts of bacterial growth. Theentire mass is shelf stable under storage conditions but is slowlysoluble in an aqueous or mammal body fluid medium and can containmedication' or other additives which are slowly released into theaqueous medium during dissolving of the mass.

The plastic mass has various advantageous properties. Preferably itisnontoxic and its plastic characteristics permit ease of molding, e.g.,by injection molding, extrusion, compression molding and casting insheet form. It can be tacky to the touch when moistened and can make agood adhesive. The mass can be edible where the base material is FDA.approved for human consumption. Most important, the mass is absorbed bythe chemicalprocesses of the human body as it becomes dissolved. Where asynthetic colloid gum, e.g., carboxymethyl cellulose gum, is used inmaking the reaction product, the resulting mass does not support anybacteria growth. Where a natural alginate gum is used, only very littlebacteria growth, if any, is evident and can be eliminated by including asmall amount of preservative such as methyl parsept. The crosslinkedalginate gum gels are further advantageous in that they have a tendencyto become tacky or tackier with slight swelling at external human bodytemperature and moisture conditions, but they nevertheless retain theirproperties at elevated temperatures. For example, such gels retain theirexcellent properties even after a high-temperature accelerated agingtest in an oven at 250 C., 15 p.s.i., for 2 hours with no changewhatsoever, indicative of their excellent shelf life.

The gums used herein support substantially less bacteria growth thandoes Karaya. Especially useful are the normally solid particulate orpowdered synthetic cellulose gums such as carboxymethyl cellulose,water-soluble salts of the cellulose gums and the particulate orpowdered natural alginate gums. Such alginates are available as drypowders from Kelco Company, San Diego, cat, under the trade namesKeltrol and Kelcoloid. Keltrol is reported to be a xanthin gum productand is classified as a carbohydrate. It is a complex polysaccharide gumhaving a molecular weight of more than 1 million. The polymeric moleculeis believed to be linear in structure with beta linked backbonescontaining d-glucose, d-manose and dvglucoronic acid groups withapproximately one d-manose side chain unit for every eight sugarresidues and one d-glucose side chain .residue for every 16 sugarresidues. The polysaccharide structure is partially acetylated andcontains pyruvic acid attached to the glucose side chain residue. Themolar ratio of d-glucosezd-manose:d-glucoronic acid is reportedto beabout 2.8:3.0:2.0.

The alginate can be any of the water-soluble alginates including thealkali metal (sodium, potassium, lithium, rubidium and cesium) salts ofalginic acid, as well as the ammonium salt, the magnesium salt and thesoluble alginates of an organic basesuch as mono-, di-, ortri-ethanolamine, aniline and the like. Also useful are the substitutedalginates such as the phospho-alginates. Such soluble alginates can beprepared by methods well known in the art such as those in U.S. Pat.Nos.

-l,8l4',98l, 2,036,922, 2,039,934, 2,097,228 and 2,128,551.

For background-material with regard to such alginates, attention is alsodirected to Steiner U.S. Pat. Nos. 2,441,729 and 2,426,125, Steiner etal. 2,463,824, and Gates U.S. Pat. No. 2,420,308. The above patents arehereby incorporated herein 'by reference so far as they disclose aginates and their manufacture, any of which soluble alginates can beused in .ac-

cordance with the present invention. The preferred alginates are thesodium and potassium alginates.

The suitable cross-linking agents are water-soluble polyols andespecially useful are alkylene glycols such as propylene glycol,butylene glycol, ethylene glycol, triethylene glycol, and glycerin.Preferably the polyols are nonaqueous," containing their normalhydroscopically absorbed water content, e.g., up to percent. Added waterin minor amounts less than 50 percent can be used although added wateris not preferred. The polyols should be reactive with the gum,preferably at room temperature, for purpose of cross-linking the gum.The preferred polyols are those providing a cross-linking chain lengthof at least three atoms, usually carbon or carbon and ether oxygenatoms, exclusive of terminal oxygens from reacted terminal hydroxyls.The water-soluble polyol crosslinking agent is used in an amountsufficient to cross-link the gum but it can also be used in an excessover and above the cross-linking amount so that it also serves as theliquid medium in which is included or occluded as part of the finalgelled or solidified mass. When used only for cross-linking purposes,usually 0.5 to 2 or 3 parts polyol per part by weight gum will besufficient although amounts within a broader range such as 0.1 to 10parts per part by weight gum can be used depending on the amount ofcross-linking desired and the amount of cross-linking agent which is tobe used as an excess to also supply the liquid medium. In the preferredcompositions about 0.5 to 6 parts polyol per part of gum are used and0.15 to 2.5 parts per part gum are especially preferred.

The liquid medium is a water-soluble organic compound which ispreferably nontoxic and which is nonreactive with the cross-linkedreaction product once the reaction product has become fullycross-linked. As noted above, the cross-linking agent, which is reactivewith the gum but not with the fully cross-linked reaction product, canadvantageously be used as the liquid medium. Other organic compounds canalso be used in lieu of or as a supplement for the excess cross-linkingagent. Glycerin-has been found to be an excellent liquid medium for thecross-linked alginates and for certain cross-linked carboxymethylcellulose gums while propylene glycol is very suitable for use both as across-linking agent and a liquid medium. Increasing the amount ofglycerin in the composition correspondingly increases the tackiness ofthe gel up to the point where the gel can no longer hold the amount ofglycerin used. The preferred compositions contain at least some glycerinin the liquid medium for improved tackiness. The liquid medium willusually be present in an amount between 0.5 and 40 parts by weight perpart by weight of total alginate and/or the cellulose gum. Preferably,the liquid medium is present in amounts between 1 and parts by weightper part gum and in especially preferred compositions the amount isbetween 2 and 10 parts by weight per part by weight gum. In cellulosegum compositions, if glycerin is not used as a liquid medium, it hasbeen found advantageous to include a small amount of glycerin, e.g.,about 0.1 up to about 0.5 parts per part by weight cellulose gum, tofunction as a wetting agent for the cellulose gum. Although somecellulose gums are highly reactive toward glycerin, some such gums arecompletely nonreactive and where a highly reactive gum is used, it hasbeen found advantageous to dilute the gum with a nonreactive gum andthereby prevent undue reaction between the glycerin and reactive gumwhen the glycerin is added to the gum powders as a wetting agent.

In some compositions where more body and more complete gelling isdesired, it is advantageous to include starch as a filler. The starchappears to initially function as a gelling agent giving the formulationa higher viscosity but then, at least in the case of the alginates,appears to retard the reaction of the alginate with the cross-linkingagent. After cross-linking is complete, the starch imparts a more rigidgel structure to the cross-linked mass. Any of a variety of starches,such as wheat starch, corn starch, potato starch and gelatinizedstarches, as well as proprietary starch compositions which are sold forgelling purposes, can be used. When starch is used, it will usually beincorporated in an amount between 0.05 and 1 part by weight per part byweight total liquid medium and crosslinked gum and in especiallypreferred starch-containing compositions it is used in an amount between0.l or 0.25 and 0.5 parts by weight based on total liquid medium andcross-linked gum.

Although it has been found that the synthetic carboxymethyl cellulosegums generally react readily with the crosslinking agent at ambienttemperatures, in the case of alginates it is sometimes desired to speedthe reaction by using a catalyst or accelerator. In other cases wherethe reaction proceeds too fast, it may be desired to retard the reactionwith an inhibitor or even slow down the function of a catalyst where acatalyst is used. The cross-linking reaction appears to be exothermic inall cases so that cooling the reacting mass may be useful to slow thereaction. However, it is desired to carry the reaction out at ambient orroom temperatures so it is preferred to regulate the reaction withcatalysts, inhibitors and the like, rather than by control of thereaction temperature. Accordingly, I have found that the reactionusually proceeds slower at a lower pH, e.g., below 3 and faster at ahigher pH, e.g., above about 8, so that small amounts of acids and basescan be used to control the reaction to some extent, I have further foundthat aluminum and calcium salts, such as aluminum hydroxide, calciumcarbonate and calcium chloride, are excellent catalysts, as are buffersalts such as sodium benzoate, for speeding up the cross-linkingreaction especially where alginates are used as the gums. Wherecatalysts are used, they are preferably used in the range of from 0.2 to2 parts by weight, and more often about 1 part by weight, per part byweight alginate.

Although the cellulose gums do not support bacterial growth and thegrowth-supporting properties of the alginate gums used in the presentcompositions are minimal to nonexistent, to be on the safe side it issometimes advantageous to include a preservative such as sodium benzoateor methyl parsept or other well-known preservatives in an amount betweenabout 0.05 and about 0.5 percent, e.g., about 0.1 percent, based ontotal composition. The use of a preservative is especially advantageouswhere Karaya is included in the composition in addition to the celluloseor alginate gum because Karaya has been found to support bacterialgrowth, although with some Karaya-containing compositions no amount ofparsept or other preservative will completely eliminate bacteriaalthough it will inhibit bacteria growth.

In some compositions designed for specific purposes it may be desirableto provide nutrient value in the composition to promote bacterialgrowth. For example, the present gels can be used as media for bacterialstudies and it may be desired to provide a low-controlled nutrient valuein the composition. This can be done by making the composition withalginate gum or mixtures of alginate gum and carboxymethyl cellulosegum, with the alginate gum present in an amount directly proportionalwith the desired nutrient value. If still greater nutrient value isdesired for bacterial growth, i.e., above and beyond what is provided bya composition made solely from alginate gum, Karaya can be added to thereaction mass in whatever amount is needed to provide the additionalnutrient value. In such compositions, parsept or other preservative isusually omitted. In this manner compositions having predetermined orcontrolled nutrient values over a wide range can consistently beprepared.

The following are more specific examples of compositions which can bemade in accordance with the present invention:

EXAMPLES 1 THROUGH 19 For each of Examples 1 through 19, the materialsindicated in Table I for each example, with the exception of thepropylene glycol, were added to and blended in a dough mixer or blenderand after the ingredients were thoroughly mixed, the propylene glycolwas added and a so blended in. The reaction proceeded and appeared to beexothermic and within about one-half hour, more or less, the materialsformed a gel. EXAMPLE 21 Each example was permitted to stand at roomtemperature for 24 hours The procedure of Example 20 was repeated exceptthat TABLE I Example l 2 3 4 5 6 7 8 9 10 11 i 12 13 14 15 16 17 18 19Ingredients: Y i

Benzoic acid Instant clearj e1 starch 3 Potato starch Corn starch...

1 Sodium alginates. 2 Carboxymethylcellulose. 3 100% food starch.

Of the above, the compositions of Examples 1 through 4 set parts byweight Kelcoloid were substituted for the 10 parts by up to good firmgels and were rated very good products. It was weight Keltrol. notedthat when the product of Example 3 was moistened, it

did not become slippery as did the products of Examples 1 and EXAMPLE 22The composhioh of Example1 was capable of suPponihg Fifteen grams ofKlugelMF were blended with 10 grams of bacterial growth. The compositionof Example 5 had only fair CMC in a dougtmype mixer Six grams ofglycerin were body but the body was better than when Kenya was usedadded and mixed into the blend to wet the carboxymethyl celalone.Examples 6 through 8 were all very good products and Mose particles and40 grams of propy|ene glycol were the the Products of Examples 9 through11 also looked Very good added and mixing was continued until thecomposition was and did not become PP 'Y when damPehed- Examples 9uniform. 0.05 gram of methyl parsept preservative were dry through 11illustrate that various different types of starches blended with thecarboxymethyl cellulose can be used. In Examples 2, 3, 6 and 7, thecalcium carbonate Th o ition prepared by Examples 20 through 22 andbenZOi ci increased the l'eaetloh Tale COmPOShiOhS were sent to anindustrial testing laboratory for eye irritation about the Same as thatof Example 6, with the exception that tests on rabbits. The followingtest procedure was used in the varying amounts of calcium chloride weresubstituted for the evaluation f h f h form lation bBl'iZOlC acid, werealso prepared and calcium chloride alone A group of five New Zealandtrain albino rabbits was used was found to also speed up he r fl I ninthe Calcium to evaluate the eye irritation properties of the testmaterial. chloride runs, the calcium chloride was premixed dry with the40 Th test h d l d was patterned fter one d ib d alginate and the y mixwas sifted into the glycol during by Draize et a1., Methods for theStudy of irritation and Toxing to minimize the possibility of thecalcium chloride settling i ity of Substances Applied Topically to theSkin and Mucous out. The above and other examples also showed that, witha M b j l f Ph m ti l d E i l given formulation, the maximum amount ofglycerin or other Th y, 82, D 4, 1944 I th t 100 mg f h i f liquidmedium for a homogeneous gel can be readily the test material wasinstilled into the conjunctiva] sac of the established simply by tryingdiffer nt amounts. If a Soli gel right eye of each test rabbit. The lefteye of each animal was product is desired, the amount of liquid medium hl be used as ascoring control. After 1 minute, 1 hour, 24 hours, 72 keptlow enough to be locked in by the cross-linked structure h r d 7 d hcornea, i i d conjunctiva were asit forms. amined and graded forirritation and injury according to a Af r s andi g for 2 hours, the mp in pr p r in standard scoring system described by Draize et al. Under theExample 12 had very good body and very good tackiness and scoringsystem, the maximum possible score for any one exthe composition ofExample 13 had better body but no as amination at each scoring period is110 points which indicates much tackiness of Example 12 indicating thateither an inmaximal irritation and damage to all three ocular tissues.Zero crease in the starch content or a decrease in the alginate conscoreindicates no irritation whatever. The scoring system tent or bothincrease the tackiness of the molded composition. Used iSgi in TableExample 14 which had a very soft body but very good tack furtherillustrates this in that the alginate content was further TABLE II.EYEIRRITATION TESTALBINO RABBITS decrefised- Example 15 took a while longerthan a 24-hour Scale of Weighted Scores for Grading the Severity ofOcular Lesions standing period to develop reasonably good tack. Example16 I. Cornea: is aliiotlzier COUZPOSKIOII having very soft body and verygood A. oplecity de fee?! density (area which is most dense is tac an isuse ul mainl f r d til en Orrea 11g 1 of Exam les 17 th a heavepurpoiles T grqducts Scattered or diffuse area-details ofiris clearlyvisible 1 b P s fi a F g; g 8 5 an did not lEasttly diseiernibletranslucent areas,details oliris slight- 0 ecome s lppery w en wet. epot 1 e or t ese compositions Y 0 Scum ils fii.islbl,sieof ii afteraddition of the propylene glycol was noticeably shorter g iii fiigiffiffif ffif ffi i f f f 3 than that of other compositions which didnot contain calcium B q iris galg 4 carbonatle illustratirig thatealciltlim carbpnzte was functioning ififi gfiif :1 et ngt fir al "5. 1g as a cata st or acce erator ort e crossin in Waterman one (1118f I1659 an y g reacnon greater than 1ehe-itlalf bi? less thtan threequarters i rcaterthan ree qua! ers up ow l0 earea EXAMPLE 20 nlqciioreequalsa X B X 5. Total rriaximurn=80 r s: Flfty parts-by weightglycerin were mixed with 20 parts by A-veluesl Folds abovenormal,congestion,swelllng,circumcornea1 welgm Propylene glycol 1977Parts y weight Instant injection (anyoralloltheseorcomblnationoianythercclear gel starch was slumed into themixture followed by 10 ghlrls st i ilrea ctlr t p l g ht(81 151 511rgggoglzgosisgsi 1 0 IT e e parts by weight Keltrol and the compositionwas mixed until 83,5 63 thoese fig g uc uniform. The composition wasthen poured into molds; and In eq z lsrtxfi.Totalrnaxlmum= was permittedto set at ambient temperatures for 24 to 48 .3,,Z "8gpalpebralconjunctivaonly)2 hours. I Vessels definitely injected abovenormal 1 I A H I ll. lrlyc Irritation Test- Albino Rabbits- Con.

More difluse, deeper crimson red individual vessels not easilydiscernible. Diffuse beefy red. B. Chemosis:

bAny s)welling above normal (includes nictitating memrane Obviousswelling with partial eversion oi the lids Swelling with lids about halfclosed Swelling with lids about half closed to completely closed 0.Discharge:

Any amount diflerent from normal (does not include small amount observedin inner canthus of normal animals) 1 Discharge with moistening of thelids and hairs just adjacent to the lids Discharge with moi =tening ofthe lids and hairs and considerable area around the eye 3 Score (A+B+C)X2. Totalmaximum= 20 Nora.lfhe maximum total score is the sum of allscores obtained for the cornea, iris and conjunctiva.

The results of the tests are recorded in Table III as averages It willbe noted from Table II that the classification system places specialemphasis on irritation or damage to the cornea and correspondingly lessstress was placed on conjunctival and iridal effects.

In the rabbit tests of Examples 20-22, transient conjunctival irritationwas noted 1 minute after installation in each case and at the 1-hourpoint iridal irritation was also noted in two rabbits for the Example 20tests and in three rabbits for the Example 22 tests. In all examples,the ocular tissues returned to normal within 24 to 72 hours.

EXAMPLES 23 AND 24 Using the procedure of Example 23, compositions weremade from the following ingredients:

Example 23 Example 24 20 grams Klugel MF grams CMC-7MF 6 grams glycerin40 grams propylene glycol 0.05 gram methyl parsept 25 grams Klugel MF 6grams glycerin 50 grams Propylene Glycol 005 gram Methylparsept BothExamples 23 and 24 set up quickly and the examples illustrate additionalnonstarch containing formulations. Both also had good adhesiveproperties.

A hand lotion was prepared by adding the gelled reaction product ofExample to an oil/water emulsion of the type normally used in thepreparation of lotions, until the desired lotion thickness orconsistency was reached. No lanolin or other wax was used in thecomposition.

A series of compositions was prepared using the basic formulation ofExample 20 but with the pH of the reaction system adjusted to variousvalues from 3.5 to 12, using additions of benzoic acid or lime as neededto adjust the pH. The pH values used are shown in the chart in FIG. 4.Immediately after mixing a sample of each composition was run through aGeneral Electric-Zahn Viscosimeter (Cup size: 44 cc., No. G with anO.l68-inch orifice) and each had approximately the same flow rate,requiring about 3 minutes to flow through the viscometer. Thecompositions were then observed l hour later and the four compositionsprepared at pHs of 7, 7.5, 8 and 8.5 had already formed a soft solidtacky gel. At 2 hours after mixing the samples of the compositions wereagain visually observed and were run through the viscometer. Thecompositions formed at pHs 6 through 9.5 were very hard gels which wouldnot run through the viscometer within 8 minutes. The samples at pH 5.5and 10 were semirigid and the samples at pH 3.5, 4, 5, II and 11.5 hadnot formed a solid gel. The viscometer flow times for each sample tested2 hours after mixing are shown in the chart of FIG. 4. Another set ofsimilar compositions was prepared using acetic acid in place of thebenzoic acid and the gel results were similar. Thus, where a solidifiedgel is desired, it should be prepared at a pH in the range of 5.5through ll, hard at 6 through 9.5 and progressively softer therebeyonddown to at least 3.5 and up to at least 12.

A variety of different types of plastic gels having differentconsistencies, adhesiveness and other physical properties, can beprepared according to this invention. As guide lines toward specificdesired properties, adhesiveness appears to be greater when cellulosegums are used than when the alginates are used and the use of starchalso apparently tends to increase adhesiveness. The body of the gel canbe regulated to some extent by regulating the amount of diluent orcarrier included within the gel. Catalysts and pH adjustment also tendto increase the body of the gel and catalysts provide a faster cure timeespecially in the case of alginates. Where bacterial growth is to becompletely eliminated, the synthetic carboxymethyl cellulose gum shouldbe used or, where alginates are used, a small amount of preservativeshould be added. Inclusion of Karaya correspondingly decreases theefficiency of the alginate or cellulose gum to an extent directlyproportional to the amount of Karaya used, and although Karaya can beaccommodated in the compositions, e.g., up to about percent or percentof the total gum, it should not be used to fully substitute the alginateor cellulose gums. I prefer to use no more than 50 percent Karaya basedon total gum. Karaya increases bacteria growth, decreases gel shelf lifein that it hardens on aging and decreases adhesiveness of thecomposition and can be used when these effects are either desired or ofno consequence in the intended use.

An important aspect of the present invention is the ability to produce aproduct which has the same beneficial characteristics and physicalproperties as Karaya and possesses additional properties which lends theproduct to less limited possibilities of application in the field ofmedicine, the food indus' try, dentistry, veterinary medicine andcosmetics. For example, compositions of the present invention can beproduced which are tacky to the touch and when moistened make goodadhesives. The physical mass of the gel lends itself to injectionmolding techniques for producing forms of various shapes. The materialis nontoxic to man, water-soluble, edible and the base materialprecursors are F.D.A. approved for human consumption, and thecomposition is completely absorbable by the chemical process of a humanor other mammal body. Especially where cellulose gum is used in makingthe products, tlie product has the additional ability of supportingabsolutely no bacterial growth. Even when alginates are used, only verylittle bacterial growth can be supported by the composition. In eithercase to be absolutely safe, a small amount of preservative can be addedto overcome any tendency toward supporting bacterial growth.

During manufacture of the compositions, concentrations of antibiotics,drugs, antibacterial agents, and/or cosmetics can be included whileproducing a solid rubbery mass. The material can then be applied to thebody, either animal or human, or inserted into the body either throughsurgery, suppositories, injections or oral means and its unusualproperty of being slowly dissolved and accepted by the body permits atime effect treatment and more effective localized treatment. Manyspecific applications such as use in suppository bandages forhemorrhoidectomies, thyroid treatment, injection suppositories fortreatment of the prostate, packing material to prevent loss of muscletone during healing after removal of an eye, packing for broken noses.As a more specific example, a molded ring such as shown in the drawingcan be used in colostomy, ileostomy and related applications by applyingaround the stomal to seal an appliance to the skin in such a way thatstoma] discharge is kept off the patients skin while promoting healingof skin which may be excoriated from stoma] discharge.

In the field of dentistry, the material can be used to fill pockets leftfrom tooth extractions and can also be formulated as a dental adhesive.Body lotions for skin treatment can also be provided by this inventionby replacing the lanolin or other wax material in the lotion emulsionsystem with the gelled reaction product.

The material is also suitable for skin treatment to treat burns, bedsores, and other conditions, adhering to the skin via its adhesiveproperties and preventing contamination and lessening the possibility ofbacterial infection while providing drug treatment against toxicpoisoning using the time effect treatment characteristics of thematerial. Additionally, the material can be molded in the form ofimplements or devices for internal or external use, e.g., birth controldevices, dissolvable valves, dissolvable catheters and dissolvablebypass tubes which could be used during surgery and later dissolved bythe body. The present compositions are quite useful in the above areasof application on or in animal bodies for experimental purposes to testeffects of various drugs or medication on the animal or on a particulardisease, as packing in organ transplant experiments, treatment of oganic disgrders and other uses.

1 claim:

1. The method of manufacturing a plastic product which comprisesreacting a hydrophilic colloid selected from the group consisting ofalginate gum and carboxymethylcellulose gum with propylene glycol as across-linking agent in an organic water-soluble liquid medium selectedfrom the group consisting of propylene glycol and glycerin until theglycol cross-links the gum to a plastic consistency.

2. The method of claim 1 wherein said liquid medium is glycerin 3. Themethod of claim 1 wherein the reacting mass includes from 0.2 to 2 partsby weight of a catalyst selected from the group consisting of calciumcarbonate, calcium chloride, sodium benzoate, benzoic acid and aluminumhydroxide.

4. The method of claim 3 wherein said catalyst is aluminum hydroxide.

5. The method of claim 3 wherein the catalyst is selected from the groupconsisting of calcium carbonate and calcium chloride.

6. The method of claim 3 wherein the catalyst is selected from the groupconsisting of benzoic acid and sodium benzoate.

7. The method of claim 1 wherein the pH of the reaction mixture is aboveabout 5.

8. The method of claim 7 wherein the pH of the reaction mixture is belowabout 1 l.

9. The method of claim 1 including the step of including starch in thereacting mass in an amount in the range of l0 to 50 wei ht percent basedon total carrier and cross-linked gum.

0. e method of claim 9 including the step of precoatrng the starch withwetting agent before its inclusion in the reaction mass.

11. The method of claim 1 including the step of mixing medication withthe colloid and polyol prior to gelling of the reaction mass.

12. The method of claim 1 including the step of molding the reactionmass to a form.

13. The method of claim 12 wherein said molding step comprises extrudingthe reaction mass as it is gelling to plastic consistency.

14. The method of claim 1 including the step of adding the gel to alotion base water emulsion until the emulsion is brought up to creamyconsistency.

2. The method of claim 1 wherein said liquid medium is glycerin.
 3. Themethod of claim 1 wherein the reacting mass includes from 0.2 to 2 partsby weight of a catalyst selected from the group consisting of calciumcarbonate, calcium chloride, sodium benzoate, benzoic acid and aluminumhydroxide.
 4. The method of claim 3 wherein said catalyst is aluminumhydroxide.
 5. The method of claim 3 wherein the catalyst is selectedfrom the group consisting of calcium carbonate and calcium chloride. 6.The method of claim 3 wherein the catalyst is selected from the groupconsisting of benzoic acid and sodium benzoate.
 7. The method of claim 1wherein the pH of the reaction mixture is above about
 5. 8. The methodof claim 7 wherein the pH of the reaction mixture is below about
 11. 9.The method of claim 1 including the step of including starch in thereacting mass in an amount in the range of 10 to 50 weight percent basedon total carrier and cross-linked gum.
 10. The method of claim 9including the step of precoating the starch with wetting agent beforeits inclusion in the reaction mass.
 11. The method of claim 1 includingthe step of mixing medication with the colloid and polyol prior togelling of the reaction mass.
 12. The method of claim 1 including thestep of molding the reaction mass to a form.
 13. The method of claim 12wherein said molding step comprises extruding the reaction mass as it isgelling to plastic consistency.
 14. The method of claim 1 including thestep of adding the gel to a lotion base water emulsion until theemulsion is brought up to creamy consistency.